Gibson Dan, HUJI, School of Medicine - IMRIC, School of Pharmacy- Institute for Drug Research

Categories:

Life science and biotechnology

Technology Keywords:

Oncology, cancer drug resistance , chemotherapy, prodrug

Development Stage:

Preliminary POC with supporting in-vivo data

Application

Although FDA approved Pt(II) drugs are used in 50% of all chemotherapeutic regimens, their inability to overcome acquired resistance, necessitates development of improved drugs. Clinicians attempt to overcome resistance by using combination chemotherapy.

The drawback of combination chemotherapy is that each of the drugs has a different pharmacokinetic profile complicating overall control.

Our Innovation

The researchers developed a novel Pt(IV) based prodrug that simultaneously releases four different bioactive moieties inside the cancer cell acting like a “cluster bomb”.

The release of several bioactive moieties that act on different cellular targets by different mechanisms, increases the chances of killing the cancer cells and overcoming resistance to cisplatin. This reaches the effect of combination chemotherapy in a single molecule.

Advantages

The lead compound releases two potent Pt(II) complexes that act by fundamentally different mechanisms as well as two bioactive ligands (DCA and PhB) that act on different cellular targets ( “cluster bombs “).

This multiple attacks on different cellular targets by a single moiety may overcome the limitations of classical combination therapy as well as resistance to cisplatin

The Opportunity

The development represents a paradigm shift from the classic approach of the “magic bullet” of Ehrlich to a “cluster bomb” approach of multiple attacks on different cellular targets by a single moiety which may overcome the limitations of classical combination therapy.

The researchers seek to synthesize a library of “cluster bombs” that will be screened against a panel of different cancers characterized by a diverse grade of sensitivity/resistance to classical chemotherapeutic drugs. This will enable us to address multiple types of cancers.